Determinants of pulmonary function improvement in patients with scleroderma and interstitial lung disease.

BACKGROUND: In patients with scleroderma-related interstitial lung disease (ILD), improvements of pulmonary function have been reported after treatment with cyclophosphamide (CYC) alone or CYC and high-dose steroids. The study objective was to identify therapeutic regimen that alone or in combination with laboratory or clinical characteristics were associated with pulmonary function improvement in these patients. METHODS: Scleroderma patients with ILD and serial pulmonary function measurements were retrospectively analyzed. We recorded forced vital capacity (FVC, % predicted), diffusion capacity (DLCO, % predicted), type of therapy, and various clinical and laboratory parameters. Treatment with IV CYC was recorded as cumulative dose (grams) and treatment with steroids as high or low dose; outcome was defined as a sustained increase in FVC (% predicted) >or= 10 points. RESULTS: Of the 59 patients who were included in the study, 29 (49 %) patients received IV CYC (cumulative dose 13.9 +/-6.2, range 5.2-26.2 gr) for 3.3 +/- 2.4 years (range 5-60 months). Eighteen out of 59 (30 %) patients received high-dose prednisolone and 41 (70 %) received low-dose prednisolone. In an ordinal logistic model, patients receiving > 12 gr of CYC were 6 times more likely to improve FVC than to decrease or maintain FVC, compared to those who did not receive CYC (p = 0.02). In multivariate analysis, the effect of high dosage CYC on FVC persisted (OR 10.82, p = 0.02). Steroid dosage (high or low) was not associated with FVC improvement (p < 0.05). CONCLUSION: In patients with scleroderma and ILD, treatment with CYC is the only variable that is independently associated with pulmonary function improvement and that prolonged (> 1 year) CYC therapy increases the probability of pulmonary function improvement more than shorter CYC courses.